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Biomedical subjects

M Rosenfeld

Publications and source records attributed to M Rosenfeld.

At least 19 recordsLinked to original sources

Electrogram configuration and detection of supraventricular tachycardias by a morphology discrimination algorithm in single chamber ICDs.

BACKGROUND: Inappropriate ICD therapy for supraventricular tachycardia (SVT) remains a significant problem. A morphology-based algorithm (Wavelet) compares baseline and tachycardia electrograms (EGM). For this analysis different EGM sources can be programmed. This study evaluates the performance of Wavelet using two different EGM configurations (SVC-Can and RV-Can) for the detection of exercise-induced SVT. METHODS: Patients with a Medtronic model 7230 single chamber ICD and a dual coil lead were included. For each EGM source (SVC-Can or RV-Can), a baseline EGM template was acquired and the morphology similarity to this template (match percentage) was evaluated for 10-15 beats at different heart rates during exercise testing. The lower VT detection limit was programmed to 600 ms (therapies off). RESULTS: A total of 28 patients (66.9 +/- 4.7 years, 93% men) and 5,824 intracardiac QRS complexes were analyzed. With the RV-Can source, a consistently high similarity to the baseline EGM template was observed (< or =100 bpm: 90.90 +/- 0.56%; >100 bpm: 90.24 +/- 0.55%, P > 0.05). In contrast, SVC-Can was associated with a lower match percentage at baseline and a significant decrease at higher heart rates (< or =100 bpm: 77.91 +/- 2.65%; >100 bpm: 59.05 +/- 5.65%, P < 0.005). Accordingly, the specificity for appropriate detection of exercise-induced SVT was higher with RV-Can (21/21 episodes) than with SVC-Can (8/18 episodes, specificity 100% vs 44%; P < 0.0001). CONCLUSION: The RV-Can configuration appears to be superior to SVC-Can as EGM source for appropriate SVT detection with the Wavelet algorithm.

Adult↗

Nutrient enrichment caused by in situ fish farms at Eilat, Red Sea is detrimental to coral reproduction.

Recent studies report conflicting results concerning the effects of eutrophication on coral reproduction. The present study examines reproductive effort in the brooding coral Stylophora pistillata exposed to chronic eutrophication caused by in situ fish cages (FC) in the northern Gulf of Eilat (Aqaba). Histological studies of 20 S. pistillata colonies transplanted to each of two study sites, one close to the nutrient enriched FC site and the other at a reference site (IUI), 8 km southwest of the FC site, show that, overall, corals from the FC site have a significantly higher percentage of polyps containing oocytes and testes than corals from the IUI site. However, average oocyte size and the percentage of oocytes reaching the size at which fertilization occurs (i.e., >200 microm) were both significantly greater in colonies at the IUI site compared to the FC site. As the reproductive season progressed, colonies at the IUI site exhibited a decrease in the percentage of polyps containing oocytes, concomitant with an increase in the number of polyps containing planulae, indicating successful development of oocytes into planulae. In contrast, in colonies at the FC site oocyte numbers were greatest at the end of the reproductive season, and overall, numbers of planulae were significantly lower compared with the IUI colonies, suggesting relative failure of oocyte maturation, fertilization and ensuing larval development. The significantly higher lipid content found during the reproduction season in IUI colonies compared with FC colonies corroborates this assertion. This data strongly suggest that nutrients released from the fish farms have adverse effects on successful production of larvae of S. pistillata. In view of the recent severe deterioration of the coral reefs of Eilat and their present critical state of health, the only chance for their renewal is the use of immediate, prudent and rational protection measures against all man-made perturbations.

Animals↗

Effect of brain damage and source location on left-right asymmetry of visual evoked potentials in a realistic model of the head.

The left-right asymmetry of visual evoked potentials (VEP) was studied using a realistic three-dimensional model of the head, constructed from CT scans. The integral equation describing the potential distribution due to an inner current-dipole (simulating the VEP source), inside the biological volume conductor (the head) was solved numerically using the finite volume method. The effect of several structural parameters, such as the natural head geometry, the location and orientation of the current source, and conductivity changes (simulating a brain damage) on the VEP asymmetry was examined. The results revealed that the natural anatomical asymmetry presented in a normal head induces some degree of VEP asymmetry (up to 0.42% at the occipital electrodes), yet the major cause of left-right asymmetry is due to asymmetrical location of the source: up to 6.53% in the O(2)-O(1) electrodes for an angular shift of 3 degrees to the left. It was also found that conductivity changes inside the head have a smaller effect on the VEP asymmetry (up to 3.35% in hemorrhaged brain compared to 1.96% in the normal brain at the C(4)-C(3) electrodes). These findings may help in better understanding VEP sources of asymmetry, originating not only due to cerebral functionality, but from structural parameters as well.

Action Potentials↗

The two sides of man-induced changes in littoral marine communities: Eastern Mediterranean and the Red Sea as an example.

Over the last two centuries, the marine life of the Eastern Mediterranean has been influenced by two major factors: one is beneficial, and concerns species migration, such as the opening of the Suez Canal, which enriched the impoverished eastern Mediterranean Sea with over 300 species of fish and invertebrates of Red Sea origin; while the other, a negative and possibly wider-reaching factor, is that of man-made pollution, which has induced unpredictable changes, destabilizing the biological world in both magnitude and duration. Initially cryptic, the effects caused by pollutants first occur at the biochemical and cellular levels of an organism, causing alterations and deviations from the normal, strongly mobilizing its defense systems. Conventional methodologies of ecological analyses, based on species and specimen numbers, cannot detect such alterations. Studying several mollusk populations from polluted and reference sites of the Red Sea and Mediterranean littoral of Israel, we used specific markers for in vivo and in vitro studies to expose the state of micronucleation; levels of defense transport systems such as membrane transport system of organic anions (SATOA) and organic cations (OCT); the state of the multi-xenobiotic resistance-mediating transporter (MXRtr). Based on fluorescent microscopy and microfluorometry, these markers offer powerful tools to expose cryptic changes in the affected populations and provide data necessary for planning and management to protect animal communities and preserve their biological diversity. Comparative analysis of general gene-expression in polluted and reference sites indicates that stress factors have differentially affected the various biological taxa and separated phenotypic sub-populations, producing a novel type of punctuated selection. Such factors, although negative in their influences, in some instances altering the qualities of organisms, and establishing alterations in their hereditary information, pre-adapt them to survive and succeed in new situations.

Adaptation, Physiological↗

Numerical modeling of the flow in stenosed coronary artery. The relationship between main hemodynamic parameters.

The severity of coronary arterial stenosis is usually measured by either simple geometrical parameters, such as percent diameter stenosis, or hemodynamically based parameters, such as the fractional flow reserve (FFR) or coronary flow reserve (CFR). The present study aimed to establish a relationship between actual hemodynamic conditions and the parameters that define stenosis severity in the clinical setting. We used a computational model of the blood flow in a vessel with a blunt stenosis and an autoregulated vascular bed to simulate a stenosed blood vessel. A key point in creating realistic simulations is to properly model arterial autoregulation. A constant flow regulation mechanism resulted in CFR and FFR values that were within the physiological range, while a constant wall-shear stress model yielded unrealistic values. The simulation tools developed in the present study may be useful in the clinical assessment of single and multiple stenoses by means of minimally invasive methods.

Blood Flow Velocity↗

Effect of choice of reference equation on analysis of pulmonary function in cystic fibrosis patients.

Pulmonary function is an important measure of disease severity and prognosis in cystic fibrosis (CF). It is generally expressed as a percentage of a predicted value, calculated using regression equations derived from a reference population. A number of reference equations are in widespread use. The purposes of this study were to determine: 1) the extent to which, for a given absolute FEV(1) value, percent of predicted (PPFEV(1)) values vary when derived by different reference equations; and 2) whether these differences affect conclusions of longitudinal and cross-sectional analyses. Subjects were all Caucasians 6-18 years old in the 1990 Cystic Fibrosis Foundation Registry. We found clinically important discrepancies in PPFEV(1) when calculated by the methods of Dockery et al. [Am Rev Respir Dis 1983;128:405-412] and Wang et al. [Pediatr Pulmonol 1993;15:75-78] as compared to Knudson et al. [Am Rev Respir Dis 1983;127:725-734] or Polgar and Promadhat [Pulmonary Function Testing in Children 1971; Philadelphia: W.B. Saunders]. In longitudinal analyses, the choice of reference equation resulted in varying apparent rates of decline in FEV(1). For example, among subjects ages 12-14 years in 1990, the decline in PPFEV(1) from 1990-1995 varied between 2-11%, depending on the choice of reference equation. In cross-sectional analyses, the choice of reference equation affected the distribution of subjects classified as having mild, moderate, or severe lung disease. CF physicians should be aware of the impact of choice of reference equation in both clinical care and research.

Adolescent↗

Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis.

A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.

Bronchoalveolar Lavage Fluid↗

Pressure-based simultaneous CFR and FFR measurements: understanding the physiology of a stenosed vessel.

Arterial stenosis is known to be one of the most serious cardiovascular diseases. Angiographical estimation of arterial stenosis provides limited information on the severity of the occlusion and the flow of blood through it. Hemodynamical assessment of the flow and pressure behaviour, is known to be clinically important. Hemodynamically based parameters, such as pressure based myocardial fractional flow reserve (FFR) and the flow based coronary flow reserved (CFR) were introduced to provide a much better tool for treating arterial diseases. We have developed a new method for simultaneous measurement of pressure-derived CFR and FFR. The advantage of pressure derived hemodynamic parameters is very substantial, and its relatively straightforward application in clinical setting is solid. The method has been validated by means of a computational fluid dynamics (CFD) model of the arterial stenosis and in vitro bench studies.

Algorithms↗

Defining a pulmonary exacerbation in cystic fibrosis.

OBJECTIVES: Despite the central importance of pulmonary exacerbations (PExs) as an outcome measure in cystic fibrosis clinical trials, no standardized definition of PEx exists. We conducted a prospective, multicenter study to establish a standardized PEx definition and score for use in clinical trials, based on clinical status rather than on treatment decisions. STUDY DESIGN: Subjects were 246 patients enrolled in the placebo arm of a randomized, controlled trial of tobramycin for inhalation. Physician-investigators completed PEx questionnaires on all subjects at scheduled intervals during the 6-month study, indicating new or worsening symptoms, physical examination findings, and impression of PEx status (presence or absence and severity). Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx. RESULTS: We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings; one also includes change in forced expiratory volume in 1 second over the preceding month. Both scores were sensitive and specific for predicting the presence of a PEx (sensitivity, 86%; specificity, 86%). The scores were validated in subjects in the intervention arm of the trial. CONCLUSION: We hope that the proposed PEx score might serve as a standardized outcome measure for future clinical trials in cystic fibrosis, allowing meaningful comparisons of study results.

Administration, Inhalation↗

Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis.

OBJECTIVES: To assess the serum and lower respiratory tract tobramycin concentrations (C(T)) produced by a single dose of tobramycin for inhalation delivered by a nebulizer and a compressor in patients with cystic fibrosis (CF) 6 months to 6 years of age. STUDY DESIGN: We performed a dose escalation study of serum C(T) measured before and 0.5, 1, 2, and 4 hours after a single dose of inhaled tobramycin, either 180 mg (10 patients) or 300 mg (19 patients). In a separate group of 12 patients, epithelial lining fluid (ELF) C(T) was measured by bronchoalveolar lavage 30 to 45 minutes after a 300-mg dose. RESULTS: A 180-mg dose of inhaled tobramycin produced a mean peak serum C(T) of 0.5 microg/mL (SD 0.4; range, <0.2 to 1.4 microg/mL). A 300-mg dose produced a mean peak serum C(T) of 0.6 microg/mL (SD 0.5; range, <0.2 to 1.2 microg/mL). These peak values are well below the accepted maximum trough concentration with parenteral dosing (2 microg/mL). The target ELF C(T) was 20 microg/mL, 10-fold greater than the minimal inhibitory concentration for most Pseudomonas aeruginosa isolates from very young patients with CF (2 microg/mL). Mean ELF C(T) was 90 microg/mL (SD 54; range, 16 to 204 microg/mL) and exceeded the target concentration in 11 patients. CONCLUSION: In patients with CF ages 6 months to 6 years, a single 300-mg dose of inhaled tobramycin appears to produce safe peak serum concentrations and drug concentrations in the bactericidal range in the lower respiratory tract.

Administration, Inhalation↗

Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis.

Pseudomonas aeruginosa lung infection is an important cause of morbidity and mortality in cystic fibrosis (CF). Longitudinal assessment of the phenotypic changes in P. aeruginosa isolated from young children with CF is lacking. This study investigated genotypic and phenotypic changes in P. aeruginosa from oropharynx (OP) and bronchoalveolar lavage fluid (BALF) in a cohort of 40 CF patients during the first 3 years of life; antibody response was also examined. A high degree of genotypic variability was identified, and each patient had unique genotypes. Early isolates had a phenotype distinct from those of usual CF isolates: generally nonmucoid and antibiotic susceptible. Genotype and phenotype correlated between OP and BALF isolates. As determined by culture, 72.5% of patients demonstrated P. aeruginosa during their first 3 years. On the basis of combined culture and serologic results, 97.5% of patients had evidence of infection by age 3 years, which suggests that P. aeruginosa infection occurs early in CF and may be intermittent or undetectable by culture.

Antibodies, Bacterial↗

Early intervention in whiplash-associated disorders: a comparison of two treatment protocols.

STUDY DESIGN: A prospective randomized trial in 97 patients with a whiplash injury caused by a motor vehicle collision. OBJECTIVES: The study evaluates early active mobilization versus a standard treatment protocol and the importance of early versus delayed onset of treatment. SUMMARY OF BACKGROUND DATA: There is no compelling evidence to date on the management of acute whiplash-associated disorders. The few studies describing treatment, however, provide evidence to support the recommendation that an active treatment in the acute stage is preferable to rest and a soft collar in most patients. METHODS: Patients were randomized to four groups. Active versus standard treatment and early (within 96 hours) versus delayed (after 2 weeks) treatment. Measures of range of motion and pain were registered initially and at 6 months. RESULTS: Eighty-eight patients (91%) could be followed up at 6 months. Active treatment reduced pain more than standard treatment (P < 0.001). When type and onset of treatment were analyzed, a combined effect was seen. When active treatment was provided, it was better when administered early, and if standard treatment was provided, it was better when administered late for reduction of pain (P = 0.04) and increasing cervical flexion (P = 0.01). CONCLUSIONS: In patients with whiplash-associated disorders caused by a motor vehicle collision treatment with frequently repeated active submaximal movements combined with mechanical diagnosis and therapy is more effective in reducing pain than a standard program of initial rest, recommended use of a soft collar, and gradual self-mobilization. This therapy could be performed as home exercises initiated and supported by a physiotherapist.

Accidents, Traffic↗

Can vortices in the flow across mechanical heart valves contribute to cavitation?

Cavitation in mechanical heart valves is traditionally attributed to the hammer effect and to squeeze and clearance flow occurring at the moment of valve closure. In the present study, an additional factor is considered--the contribution of vortex flow. Using a computational fluid dynamics analysis of a 2D model of a tilting disk mitral valve, we demonstrate that vortices may form in the vicinity of the inflow side of the valve. These vortices roll up from shear layers emanating from the valve tips during regurgitation. A significant decrease in the pressure at the centre of the vortices is found. The contribution of the vortex to the total pressure drop at the instant of closure is of the order of 70 mmHg. Adding this figure to the other pressure drop sources that reach 670 mmHg, it might be that this is the deciding factor that causes the drop in blood pressure below vapour pressure. The total pressure drop near the upper tip (750 mmHg) is larger than near the lower tip (670 mmHg), indicating a preferential location for cavitation inception, in agreement with existing experimental findings.

Blood Flow Velocity↗

Mouse models of C. pneumoniae infection and atherosclerosis.

Mouse models were used to determine whether Chlamydia pneumoniae establishes chronic infection of the aorta and contributes to atherogenesis. Persistent infection of the aorta occurred in 11 of 31 hyperlipidemic apolipoprotein E-deficient (apoE(-/-)) mice but not in C57BL/6J mice fed a normal diet after a single inoculation and in both models following repeated inoculation with C. pneumoniae. Repeated inoculation of C57BL/6J mice resulted in inflammatory changes in the heart and aorta in 8 of 40 of mice; however, no atherosclerotic lesion development was observed. Repeated inoculation of apoE(-/-) mice resulted in a statistically significant increase in lesion area (n=43; P=.05). Although Chlamydia trachomatis disseminated to the aorta, persistent infection was not established and no statistically significant increase in lesion area occurred. These studies suggest that persistent infection of the aorta can lead to inflammatory changes in the absence of hyperlipidemia and accelerate lesion progress in concert with hyperlipidemia.

Animals↗